Spatiotemporal distribution of glia in and around the developing mouse optic tract

Abstract

In the developing mouse optic tract, retinal ganglion cell (RGC) axon position is organized by topography and laterality (i.e., eye-specific or ipsi- and contralateral segregation). Our lab previously showed that ipsilaterally projecting RGCs are segregated to the lateral aspect of the developing optic tract and found that ipsilateral axons self-fasciculate to a greater extent than contralaterally projecting RGC axons in vitro. However, the full complement of axon-intrinsic and -extrinsic factors mediating eye-specific segregation in the tract remain poorly understood. Glia, which are known to express several guidance cues in the visual system and regulate the navigation of ipsilateral and contralateral RGC axons at the optic chiasm, are natural candidates for contributing to eye-specific pre-target axon organization. Here, we investigate the spatiotemporal expression patterns of both putative astrocytes (Aldh1l1+ cells) and microglia (Iba1+ cells) in the embryonic and neonatal optic tract. We quantified the localization of ipsilateral RGC axons to the lateral two-thirds of the optic tract and analyzed glia position and distribution relative to eye-specific axon organization. While our results indicate that glial segregation patterns do not strictly align with eye-specific RGC axon segregation in the tract, we identify distinct spatiotemporal organization of both Aldh1l1+ cells and microglia in and around the developing optic tract. These findings inform future research into molecular mechanisms of glial involvement in RGC axon growth and organization in the developing retinogeniculate pathway.

Conversations with Ray Guillery on albinism: linking Siamese cat visual pathway connectivity to mouse retinal development

“…() after making lesions in the cat retina and silver staining to track degenerating axons. We gained more traction on the topic recently; with fluorescent dye‐ and genetic labeling we investigated eye‐specific organization of the mouse optic tract (Lee et al ., ; Sitko et al ., ).…”

“…After mingling with each other in the optic chiasm, crossed and uncrossed fibers immediately segregate in the proximal optic tract (Sitko et al ., ). The molecular underpinnings of this segregation are beginning to emerge, and include dystroglycan (Clements & Wright, ), matrix molecules (Reese et al ., , ; Hornberg et al ., ), glial cells (Reese et al ., ; Lee et al ., ), and elements important for local translation of guidance proteins (Hornberg et al ., ), but a strict expression pattern associated with the ipsi‐ vs. contralateral RGC populations has not been established. Our in vitro analyses indicate that mouse ipsilateral RGCs have a greater propensity to fasciculate with their own ‘kind’ compared with contralateral RGCs (Sitko et al ., ).…”

Functional role of translocator protein and its ligands in ocular diseases (Review)

“…In adulthood, as microglia undergo a morphological transformation to a ramified cell shape, TSPO expression is barely detectable ( 94 ). There are several theories that might help explain this, including that TSPO is possibly involved in the physiological processes of microglial development ( 95 , 96 ), such as complement-mediated synapse elimination and phagocytosis of dead neurons ( 66 ). Temporary expression of TSPO may also be associated with the migration process of microglia during retina development ( 97 ), and the expression terminated when microglia reach the final site.…”

Retinal Ganglion Cell Axon Wiring Establishing the Binocular Circuit

“…In addition, both microglia and astroglia surround and penetrate the developing optic tract during early RGC extension. It is not clear whether these non-neuronal cells are passive or active determinants of ipsi-and contralateral RGC axon organization (Lee et al 2019).…”